<div style="text-align:justify;"> Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many co...<div style="text-align:justify;"> Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many countries with record-breaking numbers of new cases. Therefore, it is very important to develop a vaccine that can cause wide cross reactivity in clinical trials. At present, more than 90 vaccines are entering clinical trials and progressing smoothly, including inactivated vaccines, adenovirus-vectored vaccines and other types of vaccines. Here, we review and summarize the efficacy and potential threats of a SARS-CoV-2 vaccine. We reviewed whole-virus vaccines, adenovirus-subunit vaccines and recombinant protein vaccines and discussed the positive and negative consequences of a SARS-CoV-2 vaccine. However, there are still heated debates on the mechanism, effectiveness, and breadth of protection. In conclusion, this study can predict the risk of new coronavirus outbreaks in the future by discussing the research and development status of new coronavirus vaccines in China and other countries. Looking to the future, it is important to mine the large amount of data generated in clinical trials of universal new coronavirus vaccines to ensure that these vaccine programs are equally useful in the face of new coronavirus mutations. </div>展开更多
SARS-CoV-2 infection is a global public health threat.Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic.As expected,deaths from SARS-CoV-2 infection have dropped dramatically ...SARS-CoV-2 infection is a global public health threat.Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic.As expected,deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination.However,there are concerns over the duration of vaccine-induced protection,as well as their effectiveness against emerging variants of concern.Here,we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2(Ad C68-S).Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of Ad C68-S.Notably,neutralizing antibodies were observed up to at least six months after vaccination,without substantial decline.Single or double doses Ad C68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term(21 days)and long-term(6 months).Histopathological examination of Ad C68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection.Taken together,this study demonstrates the efficacy and durability of the Ad C68-S vaccine and constitutes a promising candidate for clinical evaluation.展开更多
Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines,the epidemic prevention and control are still challenging.Here,we employ a capsid and antige...Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines,the epidemic prevention and control are still challenging.Here,we employ a capsid and antigen structure engineering(CASE)strategy to manufacture an adenoassociated viral serotype 6-based vaccine(S663V-RBD),which expresses trimeric receptor binding domain(RBD)of spike protein fused with a biological adjuvant RS09.Impressively,the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months.Compared to the licensed BBIBP-CorV(Sinopharm,China),a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type,C.37(Lambda)and B.1.617.2(Delta).More interestingly,the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid.Given its effectiveness,the CASE-based S663VRBD may provide a new solution for the current and next pandemic.展开更多
Human adenoviruses(HAd Vs)are highly contagious and result in large number of acute respiratory disease(ARD)cases with severe morbidity and mortality.Human adenovirus type 3(HAd V-3)is the most common type that causes...Human adenoviruses(HAd Vs)are highly contagious and result in large number of acute respiratory disease(ARD)cases with severe morbidity and mortality.Human adenovirus type 3(HAd V-3)is the most common type that causes ARD outbreaks in Asia,Europe,and the Americas.However,there is currently no vaccine approved for its general use.The hexon protein contains the main neutralizing epitopes,provoking strong and lasting immunogenicity.In this study,a novel recombinant and attenuated adenovirus vaccine candidate against HAd V-3 was constructed based on a commercially-available replication-defective HAd V-5 gene therapy and vaccine vector.The entire HAd V-3 hexon gene was integrated into the E1 region of the vector by homologous recombination using a bacterial system.The resultant recombinants expressing the HAd V-3 hexon protein were rescued in AD293 cells,identified and characterized by RT-PCR,Western blots,indirect immunofluorescence,and electron microscopy.This potential vaccine candidate had a similar replicative efficacy as the wild-type HAd V-3 strain.However,and importantly,the vaccine strain had been rendered replication-defective and was incapable of replication in A549 cells after more than twentygeneration passages in AD293 cells.This represents a significant safety feature.The mice immunized both intranasally and intramuscularly by this vaccine candidate raised significant neutralizing antibodies against HAd V-3.Therefore,this recombinant,attenuated,and safe adenovirus vaccine is a promising HAd V-3 vaccine candidate.The strategy of using a clinically approved and replication-defective HAd V-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases.展开更多
Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respi...Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respiratory tract,which is the primary infection site for SARS-CoV-2.To overcome the limitations of intramuscular vaccines,we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain(RBD)of the spike protein of SARSCoV-2,named CA4-d NS1-n CoV-RBD(d NS1-RBD).A preclinical study showed that in hamsters challenged 1d after single-dose vaccination or 9 months after booster vaccination,d NS1-RBD largely mitigated lung pathology,with no loss of body weight.Moreover,such cellular immunity is relatively unimpaired for the most concerning SARS-Co V-2 variants,especially for the latest Omicron variant.In addition,this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses.The protective immune mechanism of d NS1-RBD could be attributed to the innate immune response in the nasal epithelium,local RBD-specific T cell response in the lung,and RBD-specific Ig A and Ig G response.Thus,this study demonstrates that the intranasally delivered d NS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection,compensating limitations of current intramuscular vaccines.展开更多
Cellular immune responses,particularly those associated with CD3+CD8+ cytotoxic T lymphocytes (CTL),are critical factors in controlling viral infection.Nasopharyngeal carcinoma (NPC) is closely associated with persist...Cellular immune responses,particularly those associated with CD3+CD8+ cytotoxic T lymphocytes (CTL),are critical factors in controlling viral infection.Nasopharyngeal carcinoma (NPC) is closely associated with persistent Epstein-Barr virus (EBV) infection.NPC vaccine studies have focused on enhancing specific antiviral CTL responses.In this study,three vaccines capable of expressing the EBV-latent membrane protein 2 (LMP2) (a DNA vector,an adeno-associated virus (AAV) vector,and a replication-defective adenovirus serotype 5 (Ad5) vector) were respectively used to immunize female Balb/c mice (4-6 weeks old) at weeks 0,2 and 4,either alone or in combination.Our results suggest that combined immunization with DNA,AAV,and adenovirus vector vaccines induced specific cellular immunity more effectively than any of these vectors alone or a combination of two of the three,constituting a sound vaccine strategy for the prevention and treatment of NPC.展开更多
文摘<div style="text-align:justify;"> Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many countries with record-breaking numbers of new cases. Therefore, it is very important to develop a vaccine that can cause wide cross reactivity in clinical trials. At present, more than 90 vaccines are entering clinical trials and progressing smoothly, including inactivated vaccines, adenovirus-vectored vaccines and other types of vaccines. Here, we review and summarize the efficacy and potential threats of a SARS-CoV-2 vaccine. We reviewed whole-virus vaccines, adenovirus-subunit vaccines and recombinant protein vaccines and discussed the positive and negative consequences of a SARS-CoV-2 vaccine. However, there are still heated debates on the mechanism, effectiveness, and breadth of protection. In conclusion, this study can predict the risk of new coronavirus outbreaks in the future by discussing the research and development status of new coronavirus vaccines in China and other countries. Looking to the future, it is important to mine the large amount of data generated in clinical trials of universal new coronavirus vaccines to ensure that these vaccine programs are equally useful in the face of new coronavirus mutations. </div>
基金the National Natural Science Foundation of China(No.32070933 to J.M.Lan and Y.F.Yao)the Natural Science Foundation of Shanghai(No.20ZR1463900 to J.M.Lan)+3 种基金financially the STS regional key project(KFJ-STS-QYZD-2021-12-001 to Z.M.Yuan and C.Shan)from Chinese Academy of SciencesNational Key R&D Program of China 2021YFE0201900 to C.Shan and 2021YFC0863300 to Z.M.Yuan and C.Shanthe National Key R&D Program of China(No.2021YFC0863400)funding from Institut Pasteur,Fondation Merieux and the Chinese Academy of Sciences to G.W。
文摘SARS-CoV-2 infection is a global public health threat.Vaccines are considered amongst the most important tools to control the SARS-CoV-2 pandemic.As expected,deaths from SARS-CoV-2 infection have dropped dramatically with widespread vaccination.However,there are concerns over the duration of vaccine-induced protection,as well as their effectiveness against emerging variants of concern.Here,we constructed a recombinant chimpanzee adenovirus vectored vaccine expressing the full-length spike of SARS-CoV-2(Ad C68-S).Rapid and high levels of humoral and cellular immune responses were observed after immunization of C57BL/6J mice with one or two doses of Ad C68-S.Notably,neutralizing antibodies were observed up to at least six months after vaccination,without substantial decline.Single or double doses Ad C68-S immunization resulted in lower viral loads in lungs of mice against SARS-CoV-2 challenge both in the short term(21 days)and long-term(6 months).Histopathological examination of Ad C68-S immunized mice lungs showed mild histological abnormalities after SARS-CoV-2 infection.Taken together,this study demonstrates the efficacy and durability of the Ad C68-S vaccine and constitutes a promising candidate for clinical evaluation.
基金the National Natural Science Foundation of China,China(Grant Nos.81925036 and 81872814)the Key Research and Development Program of Science and Technology Department of Sichuan Province,China(Grant No.2020YFS0570)+1 种基金111 project,China(Grant No.B18035)the Fundamental Research Funds for the Central Universities,China。
文摘Due to the insufficient long-term protection and significant efficacy reduction to new variants of current COVID-19 vaccines,the epidemic prevention and control are still challenging.Here,we employ a capsid and antigen structure engineering(CASE)strategy to manufacture an adenoassociated viral serotype 6-based vaccine(S663V-RBD),which expresses trimeric receptor binding domain(RBD)of spike protein fused with a biological adjuvant RS09.Impressively,the engineered S663V-RBD could rapidly induce a satisfactory RBD-specific IgG titer within 2 weeks and maintain the titer for more than 4 months.Compared to the licensed BBIBP-CorV(Sinopharm,China),a single-dose S663V-RBD induced more endurable and robust immune responses in mice and elicited superior neutralizing antibodies against three typical SARS-CoV-2 pseudoviruses including wild type,C.37(Lambda)and B.1.617.2(Delta).More interestingly,the intramuscular injection of S663V-RBD could overcome pre-existing immunity against the capsid.Given its effectiveness,the CASE-based S663VRBD may provide a new solution for the current and next pandemic.
基金supported by Grants from the National Key Research and Development Program of China(2018YFE0204503)National Natural Science Foundation of China(31570155,31370199)+1 种基金Natural Science Foundation of Guangdong Province(2018B030312010)the Guangzhou Healthcare Collaborative Innovation Major Project(201803040004,201803040007)。
文摘Human adenoviruses(HAd Vs)are highly contagious and result in large number of acute respiratory disease(ARD)cases with severe morbidity and mortality.Human adenovirus type 3(HAd V-3)is the most common type that causes ARD outbreaks in Asia,Europe,and the Americas.However,there is currently no vaccine approved for its general use.The hexon protein contains the main neutralizing epitopes,provoking strong and lasting immunogenicity.In this study,a novel recombinant and attenuated adenovirus vaccine candidate against HAd V-3 was constructed based on a commercially-available replication-defective HAd V-5 gene therapy and vaccine vector.The entire HAd V-3 hexon gene was integrated into the E1 region of the vector by homologous recombination using a bacterial system.The resultant recombinants expressing the HAd V-3 hexon protein were rescued in AD293 cells,identified and characterized by RT-PCR,Western blots,indirect immunofluorescence,and electron microscopy.This potential vaccine candidate had a similar replicative efficacy as the wild-type HAd V-3 strain.However,and importantly,the vaccine strain had been rendered replication-defective and was incapable of replication in A549 cells after more than twentygeneration passages in AD293 cells.This represents a significant safety feature.The mice immunized both intranasally and intramuscularly by this vaccine candidate raised significant neutralizing antibodies against HAd V-3.Therefore,this recombinant,attenuated,and safe adenovirus vaccine is a promising HAd V-3 vaccine candidate.The strategy of using a clinically approved and replication-defective HAd V-5 vector provides a novel approach to develop universal adenovirus vaccine candidates against all the other types of adenoviruses causing ARDs and perhaps other adenovirus-associated diseases.
基金supported by the National Program on Key Research Project of China(2020YFC0842600)the National Natural Science Foundation of China(82041038,81871651,and 81991491)+1 种基金the Major Science and Technology Program of Fujian Province(2020YZ014001)the Natural Science Foundation of Fujian Province(2021J02006)。
文摘Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);however,they are limited with respect to eliciting local immunity in the respiratory tract,which is the primary infection site for SARS-CoV-2.To overcome the limitations of intramuscular vaccines,we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain(RBD)of the spike protein of SARSCoV-2,named CA4-d NS1-n CoV-RBD(d NS1-RBD).A preclinical study showed that in hamsters challenged 1d after single-dose vaccination or 9 months after booster vaccination,d NS1-RBD largely mitigated lung pathology,with no loss of body weight.Moreover,such cellular immunity is relatively unimpaired for the most concerning SARS-Co V-2 variants,especially for the latest Omicron variant.In addition,this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses.The protective immune mechanism of d NS1-RBD could be attributed to the innate immune response in the nasal epithelium,local RBD-specific T cell response in the lung,and RBD-specific Ig A and Ig G response.Thus,this study demonstrates that the intranasally delivered d NS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection,compensating limitations of current intramuscular vaccines.
基金supported by the National High Technology Research and Development Program of China(Grant No. 2006AA02A229)
文摘Cellular immune responses,particularly those associated with CD3+CD8+ cytotoxic T lymphocytes (CTL),are critical factors in controlling viral infection.Nasopharyngeal carcinoma (NPC) is closely associated with persistent Epstein-Barr virus (EBV) infection.NPC vaccine studies have focused on enhancing specific antiviral CTL responses.In this study,three vaccines capable of expressing the EBV-latent membrane protein 2 (LMP2) (a DNA vector,an adeno-associated virus (AAV) vector,and a replication-defective adenovirus serotype 5 (Ad5) vector) were respectively used to immunize female Balb/c mice (4-6 weeks old) at weeks 0,2 and 4,either alone or in combination.Our results suggest that combined immunization with DNA,AAV,and adenovirus vector vaccines induced specific cellular immunity more effectively than any of these vectors alone or a combination of two of the three,constituting a sound vaccine strategy for the prevention and treatment of NPC.
